MAJOR ARTICLE

Vivax Malaria: A Major Cause of Morbidity

in Early Infancy
Jeanne R. Poespoprodjo,1,2 Wendelina Fobia,2 Enny Kenangalem,1,2 Daniel A. Lampah,1,2 Afdal Hasanuddin,3
Noah Warikar,2,4 Paulus Sugiarto,3 Emiliana Tjitra,5 Nick M. Anstey,6,7 and Ric N. Price6,7,8
1
District Health Authority, 2Menzies School of Health Research, National Institute of Health Research and Development Malaria Research
Program, and 3Mitra Masyarakat Hospital, Timika, Papua, 4International SOS, Tembagapura, Papua, and 5National Institute of Health Research
and Development, Ministry of Health, Jakarta, Indonesia; 6International Health Division, Menzies School of Health Research, and Charles Darwin
University, and 7Division of Medicine, Royal Darwin Hospital, Darwin, Australia; and 8Nuffield Department of Clinical Medicine, Centre
for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, England

Background. In areas where malaria is endemic, infants aged !3 months appear to be relatively protected from
symptomatic and severe Plasmodium falciparum malaria, but less is known about the effect of Plasmodium vivax
infection in this age group.
Methods. To define malaria morbidity in the first year of life in an area where both multidrug-resistant P.
falciparum and P. vivax are highly prevalent, data were gathered on all infants attending a referral hospital in
Papua, Indonesia, using systematic data forms and hospital computerized records. Additional clinical and laboratory
data were prospectively collected from inpatients aged !3 months.
Results. From April 2004 through April 2008, 4976 infants were admitted to the hospital, of whom 1560 (31%)
had malaria, with infection equally attributable to P. falciparum and P. vivax. The case-fatality rate was similar for
inpatients with P. falciparum malaria (13 [2.2%] of 599 inpatients died) and P. vivax malaria (6 [1.0%] of 603
died; P p .161), whereas severe malarial anemia was more prevalent among those with P. vivax malaria (193 [32%]
of 605 vs. 144 [24%] of 601; P p .025). Of the 187 infants aged !3 months, 102 (56%) had P. vivax malaria, and
55 (30%) had P. falciparum malaria. In these young infants, infection with P. vivax was associated with a greater
risk of severe anemia (odds ratio, 2.4; 95% confidence interval, 1.035.91; P p .041 ) and severe thrombocytopenia
(odds ratio, 3.3; 95% confidence interval, 1.0710.6; P p .036 ) compared with those who have P. falciparum
infection.
Conclusions. P. vivax malaria is a major cause of morbidity in early infancy. Preventive strategies, early diagnosis,
and prompt treatment should be initiated in the perinatal period.

In sub-Saharan Africa, infants younger than 34
months of age who are infected with Plasmodium fal-
ciparum are less susceptible to clinical symptoms and
severe disease, compared with older infected children
[1, 2]. This protection has been argued to be due to
innate mechanisms in infants rather than transfer of
maternal antibody [35]. However, symptomatic ma-
laria is not uncommon in young infants [68], and
severe disease is frequently reported [6, 9].
The contribution of Plasmodium vivax to malaria in
young infants is less well characterized [10, 11]. In areas
where P. falciparum and P. vivax are prevalent, infants
and young children are at greater risk of acquiring P.
vivax infection than P. falciparum infection [1215];
however, the contribution to morbidity in the first 3
months of life has been less well defined. In Timika,
southern Papua, Indonesia, where multidrug-resistant
P. falciparum and P. vivax are both prevalent, we define
the epidemiology of symptomatic illness associated with
P. falciparum and P. vivax infection in infancy, with a
focus on the first 3 months of life.

METHODS
Received 30 September 2008; accepted 9 February 2009; electronically published
13 May 2009.
Reprints or correspondence: Dr. R. N. Price Menzies School of Health Research,
Study site. The study was conducted in southern
PO Box 41096, Casuarina, Darwin, NT 0811 Australia (rnp@menzies.edu.au). Papua, Indonesia [16]. Malaria in this forested area has
Clinical Infectious Diseases 2009; 48:000000 an annual incidence of 876 cases per 1000 person-years,
 2009 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2009/4812-00XX$15.00
with a 57:43 ratio for P. falciparum versus P. vivax
DOI: 10.1086/599041 infection. Transmission is restricted to the lowland

P. vivax in Early Infancy CID 2009:48 (15 June) 000

areas. The Rumah Sakit Mitra Masyarakat Hospital in Timika
is the only hospital in this district, servicing an area of 21,522
km2 with a population of 200,000 people. High levels of an-
timalarial drug resistance are present for both species, with the
risk of failure within 28 days reaching 65% after chloroquine
monotherapy for P. vivax malaria and 48% after chloroquine
plus sulfadoxine and pyrimethamine for P. falciparum malaria;
high-grade resistance of P. vivax occurred in 16% of patients
[17].
Study population. The infant mortality rate in southern
Papua is estimated to be 68 deaths per 1000 live births [18].
During the period 20042008, infants accounted for 7.4% of
all hospital outpatient consultations, with malaria diagnosed in
14.4% of cases (P.S.; unpublished data). Because of economic
migration, the ethnic origin of the local population is diverse,
with highland Papuans, lowland Papuans, and non-Papuans all
resident in the region. Hospital policy dictates that all patients
presenting with a febrile illness should have blood film ex-
amination for malaria. Distribution of insecticide-treated nets
specifically targeted to pregnant women and those aged !5 years
started in 2007; however, there is no program for intermittent
presumptive treatment for infants.
Data collection. Data were collected from all infants ad-
mitted to the wards of Rumah Sakit Mitra Masyarakat Hospital
from 1 April 2004 through 30 April 2008. Demographic details
and diagnosis were recorded for all inpatients using a com-
puterized hospital records system (Q-Pro; PT Q-Pro Sukses
Mandiri). In addition, patients who received a diagnosis of
malaria were reviewed by a medically trained member of an
onsite research team, and additional details about their hos-
pitalizations were recorded on a standardized data form, as
reported previously [19]. Standard care was provided according
to hospital guidelines by the attending physician.
Substudy of young infants (03 months). The guardians
of any infant aged !3 months admitted with Plasmodium par-
asitemia were invited to have their child enrolled in an addi-
tional study of young infants in which a research nurse com-
pleted a more detailed questionnaire documenting the history
of illness in the infant. All young infants were examined by
either the attending physician or a research clinician, and their
clinical findings were documented. The presence of spleno-
megaly or hepatomegaly was determined by abdominal ex-
amination. Fever was defined as an axillary temperature
137.5C, and respiratory insufficiency was defined on the basis
of age-stratified criteria, as described elsewhere [19, 20]. Low
weight for age was defined as 2 SDs below the median value
of the reference (healthy) population and was further classified
as severe if it was 3 SDs below [21].
Malaria was diagnosed at the hospital laboratory by mi-
croscopy of Giemsa-stained blood films and parasite density
recorded as 1+ to 4+. Slides were considered to be negative for
000 CID 2009:48 (15 June) Poespoprodjo et al.
malaria after review of 100 high-power fields. Infants enrolled
in the more detailed survey had an additional blood film taken,
which was read by an expert microscopist; parasite counts were
determined from the number of parasites per 200 white blood
cells on Giemsa-stained thick films. Peripheral parasitemia was
calculated from the recorded white blood cell count. Slides were
considered to be negative for malaria after review of 200 high-
power fields. A thin smear was also examined to confirm par-
asite species and used for quantification if the parasite count
was 1200 per 200 white blood cells. The hospital laboratory
participates in ongoing training and quality control, with 190%
of slide recordings confirmed on cross-checking by an inde-
pendent expert microscopist [19].
Venous blood samples (15 mL) were obtained from infants
with malaria admitted to the pediatric wards for measurement
of complete blood cell counts and hemoglobin concentration
(using an electronic counter [Coulter JT]).
Malaria was defined as a symptomatic illness associated with
any peripheral parasitemia. The diagnosis of severe disease was
made in accordance with the World Health Organization cri-
teria for severe P. falciparum malaria [19, 20]. Other comor-
bidities (e.g., diarrhea, sepsis, pneumonia, and meningitis) were
diagnosed on the basis of clinical, laboratory, and radiologic
findings.
All infants with peripheral parasitemia received standard an-
timalarial therapy and supportive care, in accordance with hos-
pital protocol. Before March 2006, the local protocol for new-
born infants recommended 7 days of quinine for both P.
falciparum and P. vivax infection. After March 2006, infants
who weighed 15 kg were treated with dihydroartemisinin-pi-
peraquine for uncomplicated malaria.
Statistical analysis. Data from the questionnaire and the
laboratory were entered into an EpiData database, version 3.02
(EpiData Association). Data were analyzed using SPSS, version
15.0 for Windows software (SPSS). Infants with healthy deliv-
eries and those with malaria diagnosed from active screening
were excluded from the analysis. Normally distributed data
were compared by Students t test. Data that did not conform
to a normal distribution were compared by the Mann-Whitney
U test. Categorical data were compared by calculating the x2
with Yates correction or by Fishers exact test and the odds
ratio (OR) with 95% confidence intervals (CIs).
Ethics approval. Ethics approval for this study was ob-
tained from the ethics committees of the National Institute of
Health Research and Development, Ministry of Health of In-
donesia, and Menzies School of Health Research, Darwin,
Australia.
RESULTS
Inpatient malaria in first year of life. During the period from
April 2004 through April 2008, 4976 (12.4%) of 40,035 patients
admitted to the hospital were infants, and 1560 (10.0%) of
15,582 patients admitted to the hospital had malaria. In total,
1560 (31.4%) of 4976 infants admitted to hospital had malaria,
with infection attributable to P. falciparum in 662 infants
(42.4%), P. vivax in 668 infants (42.8%), and mixed species in
222 infants (14.2%). Eight infants were infected with Plasmo-
dium malariae. Patients of Papuan origin were more likely to
have malaria than non-Papuans (OR, 3.1; 95% CI, 2.53.9;
P ! .001), and this was apparent for all species of infection.
Although there was an overall predominance of all-cause ad-
missions for male infants throughout infancy (54.6%; 95% CI,
53.3%56.0%), female infants were at greater risk of P. vivax
infection (OR, 1.25; 95% CI, 1.061.48; P p .009) but not for
any other species of infection. Infants admitted to the hospital
at !1 month had a 9.0% (87 of 967) prevalence of malaria,
which increased throughout the first year of life to 54% (792
of 1476) in the last quarter. P. vivax was the predominant species
from birth to 8 months of age (figure 1 and table 1).
Additional clinical details were available in 1424 (91.2%) of
the 1560 infants with malaria, with severe disease (defined as
severe anemia, coma, or respiratory distress) present in 547
(38.4%) of 1424. The overall risk of severe malaria decreased
with age (P ! .001), with the risk of respiratory distress signif-
icantly greater in infants !3 months, compared with older in-
fants (OR, 9.2; 95% CI, 4.57.5; P ! .001) (table 1). The mean
hemoglobin concentration in infants who were admitted to the
hospital with malaria was 6.7 g/dL (95% CI, 6.66.9 g/dL),
compared with 9.7 g/dL (95% CI, 9.69.9 g/dL) for 1389 infants
who were admitted to the hospital without malaria during the
same period (P ! .001). The corresponding rates of severe ane-
mia were 30% (420 of 1424 infants) and 3.9% (54 of 1389
infants; OR, 13.7; 95% CI, 10.118.6; P ! .001). Infants with
pure P. vivax infection were at greater risk of severe anemia
(193 [31.9%] of 6605) than were those with P. falciparum ma-
Figure 1. Age-specific risk of malaria in patients admitted to hospital with Plasmodium falciparum (bold line), Plasmodium vivax (hatched line), and
mixed (dotted line) infections. Lines represent predicted values from a logistic regression model in which age was entered as a linear effect.
laria (144 [24%] of 601; OR, 1.3; 95% CI, 1.041.7; P p
.025), and this risk remained after controlling for age (adjusted
OR, 1.5; 95% CI, 1.161.95; P p .002). The risk of severe ane-
mia in infants was (81 [38.6%] of 210) with mixed infections,
significantly greater than that with pure P. falciparum infection
(P ! .001) but not P. vivax infection (P p .093).
During the study period, 173 deaths among infants aged 11
week were reported at the hospital, of which 23 (13.9%) were
associated with malaria. The risk of death was significantly
greater for infants without malaria (150 [4.4%] of 3416) than
for those with malaria (23 [1.6%] of 1474; OR, 2.9; 95% CI,
1.84.6; P ! .001). The overall infant mortality rate associated
with P. falciparum malaria was 2.2% (13 of 599 infants), which
is similar to the rate for P. vivax malaria (6 [1.0%] of 603) and
mixed-species malaria (4 [1.9%] of 210; P p .258).
Substudy of malaria in young infants (03 months old). Of
the 234 infants 3 months or younger who were admitted to
the hospital with malaria, 187 (76%) were enrolled in the ad-
ditional study with more detailed data collection (figure 2). No
significant difference was found in the age and sex distribution
of infants enrolled compared with those not enrolled in the
nested study. Microscopic reexamination of the admission
blood film revealed concordance between first and second read-
ings of 88% (134/152), with 6 patients (3.2%) found to be
blood smear negative. Of the 181 young infants with confirmed
malaria, P. falciparum was present in 55 (30%), P. vivax in 102
(56%), mixed infections in 22 (12%), and P. malariae in 2
(1%).
Most infants were treated with intravenous quinine alone
(93 [51%] of 181 patients), with the remaining receiving in-
travenous artesunate followed by oral dihydroartemisinin-
piperaquine (46 [25%]), oral dihydroartemisinin-piperaquine
alone (7 [4%]), oral artesunate (18 [10%]), and oral artesunate-
amodiaquine (13 [7%]). Antimalarial treatment was not doc-
P. vivax in Early Infancy CID 2009:48 (15 June) 000
Table 1. Characteristics of infants admitted to the Rumah Sakit Mitra Masyarakat Hospital (Timika, southern Papua, Indonesia) with malaria.

Patient age, months

Characteristic 01 11 to 3 13 to 6 16 to 9 19 to 12 Total P
a
Proportion of infants with malaria (%) 87/967 (9.0) 147/693 (21.2) 254/933 (27.2) 280/907 (30.9) 792/1476 (53.7) 1560/4976 (31.4) !.001
Etiology of malaria
b
Plasmodium falciparum 34 (39.1) 48 (32.7) 81 (31.9) 124 (44.3) 375 (47.3) 662 (42.4) !.001
Plasmodium vivax 42 (48.3) 85 (57.8) 132 (52.0) 122 (43.6) 287 (36.2) 668 (42.8)
Plasmodium malariae 0 (0) 2 (1.4) 0 (0) 1 (0.4) 5 (0.6) 8 (0.5)
Mixed infection 11 (12.6) 12 (8.2) 41 (16.1) 33 (11.8) 125 (15.8) 222 (14.2)
c d
Hemoglobin concentration, mean g/dL (95% CI) 7.9 (7.28.6) 6.5 (6.26.9) 6.4 (6.16.7) 6.9 (6.67.2) 6.7 (6.56.9) 6.7 (6.66.9) !.001
c
Signs of severity
e a
Severe anemia 16 (14.2) 41 (29) 75 (33) 67 (28) 221 (30) 420 (30) .32
a
Respiratory distress 31 (14.2) 61 (44) 22 (9.7) 19 (8.0) 44 (6.0) 177 (12.4) !.001
Coma 1 (1.2) 6 (4.3) 5 (2.2) 4 (1.7) 4 (0.5) 22 (1.5) .02a
c a
Mortality 2 (2.4) 4 (4.3) 3 (1.3) 3 (1.3) 11 (1.5) 23 (1.6) .349

NOTE. Data are no. (%) of infants, unless otherwise indicated.

a
Determined by x2 for trend.
b
Determined by overall x2 test.
c
Data restricted to 1424 infants (91%) for whom further details were available.
d
Determined by 1-way analysis of variance.
e
Hemoglobin concentration, !5 g/dL.

Figure 2. Profile of a study of Plasmodium vivax malaria in early
infancy.
umented in 4 young infants. Almost one-half (73 [40%] of 181
patients) of the young infants also received antibiotic treatment.
At hospital admission, 152 (84%) of 181 young infants had
fever or a history of fever, with a median duration of symptoms
before admission of 3 days (interquartile range, 27 days). Se-
vere disease was present in 128 (70%) of the 181 young infants,
splenomegaly in 86 (48%) of 181 patients, and malnutrition
in 31 (20%) of 154 patients. No significant difference was found
in the prevalence of signs or symptoms, nutritional status, or
markers of severity according to the species of infection (table
2) or between neonates and infants 13 months old.
Laboratory investigations. The geometric mean parasite
count was moderately high in both patients infected with P.
falciparum (8046 mL1; 95% CI, 310320,827 mL1) and in those
infected with P. vivax (5814 mL1; 95% CI, 41798425 mL1)
(table 2). The mean hemoglobin concentration was 6.8 g/dL
(95% CI, 6.47.2 g/dL), with severe anemia present in 52 (29%)
of 176 infants and severe thrombocytopenia (thrombocyte
count, !50,000 cells/mm3) in 33 (21%) of 159 infants. Com-
pared with infants who had P. falciparum malaria, young infants
with P. vivax malaria were at greater risk of severe anemia (OR,
2.4; 95% CI, 1.035.9; P p .041) and severe thrombocytopenia
(OR, 3.3; 95% CI, 1.0710.6; P p .036) (table 2); both ORs
remained statistically significant after we controlled for age (ad-
justed OR, 2.2 and 3.1, respectively; P p .04 ). The median
white blood cell count was 8500 cells/mm3 (range, 130062,400
cells/mm3) and did not differ according to the species of
infection.
Outcome. The median duration of hospitalization for
young infants with malaria was 4 days (range, 138 days). In
total, 7 infants (4%) died, 5 of whom had P. falciparum malaria,
and 2 of whom had P. vivax malaria. Three of these infants
died 24 h after admission to hospital. Additional details are
provided in table 3.
DISCUSSION
In Papua, severe disease and hospitalization are observed after
infection with multidrug-resistant strains of both P. falciparum
and P. vivax [19]. Previous studies in this region have dem-
onstrated that, although the prevalence of P. falciparum infec-
tion peaks among young adults aged 1525 years, the burden
of P. vivax is predominantly in children aged !5 years [16, 19].
In the present study, we highlight that the risk of admission to
the hospital with malaria with either species starts in early
infancy and is associated with hospitalization, severe disease,
and death. At the Rumah Sakit Mitra Masyarakat Hospital,
one-third of all infant admissions are associated with malaria,
with P. vivax the predominant species up to 8 months of age
(figure 1).
These findings mirror those of an associated community-
based survey in which P. vivax infection accounted for 67% of
malaria infections in infancy [16]. Prospective studies from
both Papua New Guinea and Vanuatu have previously described
the importance of P. vivax infection in young children with
symptomatic disease uncommon in adults [12, 14, 15], sug-
gesting the rapid development of immunity [22].
In regions of high P. falciparum endemicity, the risk and
morbidity from malaria in early infancy (the first 3 months of
life) are relatively low [5, 8]. In contrast, in Papua, where P.
vivax is highly prevalent, we found that malaria was present in
almost one-fifth of all-cause hospital admissions in young in-
fants, with a risk of severe disease similar to that of older infants.
Our study was restricted to infants who presented to the hos-
pital and is thus likely to have preferentially selected those with
clinical complications; nonetheless, the degree of morbidity was
striking and suggests a significant risk of infection and suscep-
tibility to severe disease. The low prevalence of severe malaria
in infants has been attributed to passive immunity from ma-
ternal antibodies and a degree of innate immunity [4, 8]. How-
ever, despite the high prevalence of maternal malaria in this
region (17%) [23] and the high prevalence of antibodies to
both Plasmodium species in adults [24], we found that im-
munity had a limited effect in preventing severe malaria from
either species in early life.
Severe anemia was the most frequent manifestation of se-
verity for both P. falciparum and P. vivax infections and was
more prevalent among infants with P. vivax infection than
P. vivax in Early Infancy CID 2009:48 (15 June) 000
Table 2. Admission characteristics and laboratory investigation of young infants (age, !3 months) admitted to the hospital with
malaria.

Plasmodium falciparum Plasmodium vivax

infection infection Mixed infection
a
Characteristics (n p 55) (n p 102) (n p 22) P
Male sex 30/55 (55) 58/102 (57) 14/22 (67) .77
Papuan ethnicity 41/55 (75) 85/102 (83) 19/22 (86) .32
Symptoms and signs
Fever and/or history of fever 46/55 (84) 85/102 (83) 19/22 (86) .94
Splenomegaly 26/55 (47) 45/101 (45) 14/22 (64) .27
Hepatomegaly 16/55 (29) 29/101 (29) 8/22 (36) .77
Sign of severity
Hemoglobin concentration, !5 g/dL 10/54 (18) 35/98 (36) 7/22 (32) .08a
Respiratory distress 29/54 (54) 62/101 (61) 12/21 (57) .64
Coma 1/54 (2) 2/102 (2) 0/22 (0) .81
b
Underweight 13/44 (29) 16/90 (18) 2/18 (11) .16
Geometric mean parasite count, mL1 (95% CI) 8046 (310320,827) 5814 (41798425) 1990 (6196393) .10
Hemoglobin concentration, mean g/dL (95% CI) 7.8 (7.18.5) 6.5 (5.96.9) 6.3 (5.27.4) .005c
Anemiad 49/54 (91) 94/98 (96) 21/22 (95) .41
Platelet count
e
Median platelets/mm3 (range) 113,500 72,500 63,000 (35,000116,000) .002
(32,000685,000) (23,000962,000)
!100,000 cells/mm3 24/51 (47) 57/88 (65) 13/18 (72) .06
a
!50,000 cells/mm3 5/51 (10) 23/88 (26) 5/18 (28) .06
White blood cell count, median cells/mm (range)3
9850 (250060,000) 8050 (130062,400) 7600 (420012,700) .06a
Leukopeniaf 6/44 (14) 5/74 (7) 4/18 (22) .14
g
Leukocytosis 10/44 (23) 7/74 (9) 0/18 (0) .02

NOTE. Data are proportion of infants (%), unless otherwise indicated.

a
P ! .05 for Plasmodium vivax versus Plasmodium falciparum.
b
Weight for age 2 SDs below the median value of the reference (healthy) population [21].
c
P .001 for P. vivax versus P. falciparum.
d
Hemoglobin concentration, !11 g/dL.
e
P p .003 for P. vivax versus P. falciparum.
f
White blood cell count, !5000 cells/mm3.
g
White blood cell count, 125,000 cells/mm3 in neonates and 115,000 cells/mm3 in children aged 13 months.

among those with pure P. falciparum infection (OR, 1.3). Al-
though severe anemia associated with P. falciparum in Africa
generally manifests after 4 months of age [25], almost one-
third of young infants in Papua were severely anemic. This is
likely to reflect a number of factors. Hookworm infection and
malnutrition reduce mean hemoglobin concentrations; how-
ever, the rates of severe anemia in infants admitted without
malaria was only 3.9% and that of aparasitemic infants in a
house to household survey was 0.6% [16], suggesting that, in
this age group, malaria was a major contributory factor. Both
P. vivax and P. falciparum cause dyserythropoiesis and hemol-
ysis, resulting in a combination of impaired red blood cell
production and loss of parasitized and unparasitized erythro-
cytes [2628]. Community studies conducted in parallel high-
lighted that only one-third of infants with malaria infections
were symptomatic [16], making it likely that many infections
remain undetected or undertreated before presentation with
worsening anemia. Persistent and recurrent infections are also
important components arising from the emergence of multi-
drug-resistant strains of both P. falciparum and P. vivax [17],
associated with repeated bouts of malaria from vivax relapses
and P. falciparum reinfections. Because severe anemia has been
shown to be an important determinant of infant mortality [6,
8], the prevalence and degree of anemia in Papua are likely
therefore to be major factors in the high infant mortality rates
reported locally (68 deaths per 1000 live births).
Another notable finding of our study was the high level of
peripheral parasitemia in the youngest infants with P. vivax
infection. P. vivax is capable of inducing fever at parasite levels
lower than those necessary to cause fever in P. falciparum in-
fection. Indeed, in associated community surveys and clinical
studies in the same area, the geometric mean P. vivax parasite
counts in clinical infections were generally 15002000 per mL1
[29, 30], with the pyrogenic threshold estimated at 400600
per mL1 [16, 23]. In infants younger than 3 months the geo-
metric mean parasite count was significantly higher (5814 per

000 CID 2009:48 (15 June) Poespoprodjo et al.

Table 3. Details of young infants (!3 months) admitted to the hospital with malaria who died.

Patient Age Sex Nutritional status Plasmodium species Other medical condition Malaria treatment Intravenous antibiotic treatment Time before death

1 6 days Female Severely underweight Plasmodium falciparum Neonatal sepsis (clinical diagnosis) Intravenous quinine Ampicillin 38 days
2 2 months Male Not recorded P. falciparum Bronchopneumonia Intravenous quinine Ampicillin, gentamicin 4 days
3 2 months 17 days Male Not recorded P. falciparum Bacterial meningitis (cerebrospinal Intravenous quinine Ampicillin, gentamicin 6 days
fluid confirmed)
4 2 months 21 days Female Severely underweight P. falciparum Coma, severe anemia, hypoglyce- Intravenous quinine Ceftriaxone Within 24 h
mia, metabolic acidosis
5 3 months Male Normal P. falciparum Severe anemia with metabolic No record of malaria treatment Ceftriaxone and gentamicin Within 24 h
and respiratory acidosis
6 1 month 11 days Male Normal Plasmodium vivax Coma Intravenous artesunate Ampicillin, gentamicin, Within 24 h
ceftriaxone
7 2 months 16 days Male Underweight P. vivax Respiratory distress and severe Intravenous artesunate and Ampicillin 4 days
anemia then oral dihydroartemisinin-
piperaquine
mL1) and similar to that observed with P. falciparum, suggesting
an inherent susceptibility to infection in early infancy, which
may reflect a lack of immunity and/or a greater propensity for
parasite multiplication.
In southern Papua, malnutrition generally manifests in in-
fants 56 months old, when mothers stop breast-feeding their
children. In household surveys, the overall prevalence of un-
derweight infants is 8% in the first year of life (M. Karyana;
unpublished data) but was significantly higher in young infants
hospitalized with malaria in our study (28% with P. falciparum
and 18% with P. vivax), a finding consistent with either P. vivax
and P. falciparum malaria contributing to malnutrition in these
young infants or with malnutrition increasing susceptibility to
malaria. Although the relationship between malaria and low
nutritional status is complex and likely bidirectional [31], our
results in young infants concur with previous studies in children
aged !2 years [32].
A limitation of the present study was the unavailability of
related details on associated comorbidities, particularly routine
microbiology. A proportion of infants with malaria are likely
to have been admitted to the hospital with alternative diagnoses
and incidental parasitemia [33]. Approximately 40% of infants
hospitalized with malaria had either leukocytosis or leukopenia,
and this did not differ significantly among species of infection.
Although sepsis itself may also have contributed to anemia [34],
malaria coinfection and its associated anemia will have un-
doubtedly contributed to the underlying associated morbidity.
In conclusion, P. vivax is associated with major morbidity
in early infancy. Malaria prevention strategies, such as insec-
ticide-treated nets and intermittent presumptive treatment for
infants, are mainly targeted at reducing the burden of P. fal-
ciparum infection [35]. However, the chronic and relapsing
nature of P. vivax infection and its early acquisition are likely
to undermine the effectiveness of these approaches. Additional
studies are needed to confirm whether the degree of morbidity
observed in southern Papua can be generalized to other vivax
endemic settings. However, in regions with mixed P. vivax and
P. falciparum endemicity, improved strategies are needed ur-
gently to reduce infection from all Plasmodium species, espe-
cially P. vivax. Our study suggests that these interventions
should be initiated in the perinatal period.
Acknowledgments
We are grateful to Lembaga Pengembangan Masyarakat Amungme Ka-
moro and the staff of the National Institute of Health Research and De-
velopment, Menzies School of Health Research, Timika, research program
for their support and advice in performing the study.
Financial support. Wellcome TrustNational Health and Medical Re-
search Council (NHRMC) (Wellcome Trust ICRG GR071614MA-NHMRC
ICRG ID 283321). J.R.P. is supported by an AusAID Australian Leadership
Award. N.A. is supported by an NHMRC Practitioner Fellowship. R.P. is
funded by a Wellcome Trust Career Development Award (074637).
Potential conflicts of interest. All authors: no conflicts.
000 CID 2009:48 (15 June) Poespoprodjo et al.
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